The long-term objective of our research is to elucidate the central mechanisms and neuroplastic processes underlying acute and chronic craniofacial pain conditions and their control. Our neuronal studies have focused on the V subnucleus caudalis since this region has been particularly implicated in craniofacial pain mechanisms and our data suggest that deep (muscle and temporomandibular joint, TMJ) nociceptive inputs evoked by the C-fiber excitant and inflammatory irritant, mustard oil (MO), are especially effective in inducing increased excitability and deep and cutaneous mechanoreceptive field expansions of rat caudalis nociceptive neurons. We have also shown that injection of MO into TM tissues can reflexly induce an increase in electromyographic (EMG) activity of the digastric and masseter muscles in rats and the reflex EMG increases appear to be modulated by NMDA and opioid receptor mechanisms. Since our preliminary data suggest the reflex EMG increases might involve a relay in caudalis, we wish to delineate the role of subnucleus caudalis and some of the specific neurochemical processes involved. We propose to test three hypotheses: The enhanced EMG activity induced by the injection of the C-fiber excitant/inflammatory irritant mustard oil into TMJ tissues involves (Hypothesis I) a pathway utilizing certain region(s) of the subnucleus caudalis, (Hypothesis II) excitatory amino acid (EAA) synaptic mechanisms operating within caudalis, and (Hypothesis III) specific opioid receptor mechanisms. I: Since we have shown that surgical or ibotenic acid lesions of caudalis can block the MO- induced EMG activity increases, we will use a) electrical microstimulation and b) glutamate microinjection within caudalis to determine which cellular region(s) of caudalis may mediate the BMG increases in the jaw muscles. II: As we have shown that systemic or i.c.v. administration of the NMDA antagonist, MK-801, can block the MO-induced EMG activity increase, we will apply to caudalis c) agonists and d) antagonists of EAA receptor subtypes, NMDA, kainate and AMPA, to determine if they respectively enhance or depress the BMG activity. III. Since we have shown that application of the opioid antagonist naloxone after the initial MO-induced EMG increase has subsided can provoke recurrence of increased EMG activity ("rekindling"), we will further characterize the opioid receptor properties involved by e) testing for stereo-specificity of the naloxone effect and f) intrathecally applying specific opioid receptor subtype (mu, kappa, delta) antagonists to see which subtype(s) is/are involved in this rekindling effect. Since neural alterations associated with injury and inflammation may be involved in many craniofacial pain conditions, including temporomandibular disorders (TMDs), the information gained from this research will provide a better understanding of acute and chronic craniofacial pain conditions.